The Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
The Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Adv Protein Chem Struct Biol. 2019;114:61-83. doi: 10.1016/bs.apcsb.2018.09.002. Epub 2018 Nov 28.
The cellular proteome performs highly varied functions to sustain life. Since most of these functions require proteins to fold properly, they can be impaired by mutations that affect protein structure, leading to diseases such as Alzheimer's disease, cystic fibrosis, and Lynch syndrome. The cell has evolved an intricate protein quality control (PQC) system that includes degradation pathways and a multitude of molecular chaperones and co-chaperones, all working together to catalyze the refolding or removal of aberrant proteins. Thus, the PQC system limits the harmful consequences of dysfunctional proteins, including those arising from disease-causing mutations. This complex system is still not fully understood. In particular the structural and sequence motifs that, when exposed, trigger degradation of misfolded proteins are currently under investigation. Moreover, several attempts are being made to activate or inhibit parts of the PQC system as a treatment for diseases. Here, we briefly review the present knowledge on the PQC system and list current strategies that are employed to exploit the system in disease treatment.
细胞蛋白质组执行着高度多样化的功能以维持生命。由于这些功能大多数都需要蛋白质正确折叠，因此，影响蛋白质结构的突变会使这些功能受损，导致阿尔茨海默病、囊性纤维化和林奇综合征等疾病。细胞已经进化出一种复杂的蛋白质质量控制系统（PQC），其中包括降解途径和多种分子伴侣和共伴侣，它们共同作用以促进异常蛋白质的重折叠或去除。因此，PQC 系统限制了功能失调蛋白质的有害后果，包括那些由致病突变引起的后果。这个复杂的系统还没有被完全理解。特别是目前正在研究当暴露时触发错误折叠蛋白质降解的结构和序列基序。此外，人们正在尝试激活或抑制 PQC 系统的某些部分作为治疗疾病的方法。在这里，我们简要回顾一下目前关于 PQC 系统的知识，并列出了当前用于在疾病治疗中利用该系统的策略。
